Diabetes represents a global health crisis. In the United States alone, approximately 29.1 million people (9.3% of the population) suffer from diabetes, resulting in direct medical costs of $176 billion (National Diabetes Statistics Report, 2014). New medicines that can restore ? cell function in these patients, thereby preventing or alleviating the debilitating consequences of the disease, are urgently needed. Although immortalized human ? cell lines have been aggressively sought by pharmaceutical companies as tools to discover such treatments, cell lines that accurately model the complex physiology of primary ? cells have not yet been developed. In response to this unmet market need, Regenerative Medical Solutions (RMS) has developed a proprietary protocol to differentiate induced pluripotent stem cells (iPSC) into pancreatic islet-like clusters (ILC) containing abundant glucose-responsive ?-like cells. These ILC represent a potentially unlimited source of human ?-like cells for use in drug discovery and testing. Using Phase I funding, RMS successfully adapted a panel of 10 iPSC lines for use in its protocol, and demonstrated that ILC made from these cells closely resemble primary human pancreatic islets in terms of both gene expression and function. In the Phase II project proposed here, RMS will move four of these iPSC lines forward into product development. Each cell line will be thoroughly characterized and banked for large-scale production. ILC derived from each cell line will be extensively characterized, and this characterization will serve as the basis for the establishment of stringent product release criteria. Production-scale culture protocols will be developed based on RMS's highly successful research-scale protocols, enabling production of batch sizes that will meet customer needs. A first-in-class cryopreserved cell product will also be developed. Finally, a suite of highly customizable live cell products geared towards high-throughput and high-content compound screening will be generated. This suite of new products will meet the strong demand among RMS's customers for physiologically accurate cell-based tools for the discovery of new medicines to mitigate the diabetes epidemic.